宁波地区新生儿先天性肾上腺皮质增生症筛查分析

Screening and analysis of newborn congenital adrenal hyperplasia in Ningbo area

目的分析宁波地区新生儿先天性肾上腺皮质增生症(congenital adrenal hyperplasia,CAH)的筛查结果,了解CAH的发病率,探讨新生儿CAH患儿CYP21A2基因突变谱,为临床诊断和遗传咨询提供参考。方法回顾性分析2018年6月—2022年6月宁波地区268319例新生儿CAH的筛查结果和发病情况;再应用Sanger测序和多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对确诊的CAH患儿进行CYP21A2基因检测,分析CYP21A2基因检测结果。结果268319例新生儿中,CAH筛查阳性1099例,阳性率为0.41%;最终确诊15例CAH,CAH发病率为0.056‰。15例CAH的患儿根据临床表型分型,失盐型13例(死亡3例),单纯男性化2例。9例确诊CAH的患儿经Sanger测序和MLPA检测,共检出11种突变,包括I2G、p.R484Pfs*58、p.Q319*、p.L308Ffs*6、p.G111Vfs*21、p.R357W、p.I173N、p.V282L、p.I237N、p.V238E和p.M240K。结论宁波地区新生儿CAH发病率为0.056‰,与全国平均水平相近;对CAH患儿进行基因检测,可明确病因,并对疾病的早期治疗,遗传咨询提供参考。

Objective This paper aims to analyze the screening results of newborn congenital adrenal hyperplasia(CAH)in Ningbo area,understand the incidence rate of CAH,and explore the CYP21A2 gene mutation spectrum of newborn CAH,so as to provide reference for clinical diagnosis and genetic counseling.Methods The screening results and incidence of CAH in 268319 newborns in Ningbo area from June 2018 to June 2022 were retrospectively analyzed.Then,Sanger sequencing and multiplex ligation-dependent probe amplification(MLPA)were used to detect CYP21A2 gene in the children with CAH,and the results were analyzed.Results Among 268319 newborns,1099 were CAH positive,with a positive rate of 0.41%;A total of 15 cases were diagnosed as CAH,and the incidence rate of CAH was 0.056‰.According to the clinical phenotype,15 children with CAH were classified as salt losing type in 13 cases(3 cases died)and simple masculinization in 2 cases.Nine children with confirmed CAH were detected by Sanger sequencing and MLPA.A total of 11 mutations were detected,including I2G,p.R484Pfs∗58,p.Q319∗,p.L308Ffs∗6,p.G111Vfs∗21,p.R357W,p.I173N,p.V282L,p.I237N,p.V238E and p.M240K.Conclusion The incidence of CAH in Ningbo area was 0.056‰,close to the national average.Genetic testing in children with CAH can clarify the cause of the disease,and provide reference for early treatment and genetic counseling.